Targeting of T lymphocytes to melanoma cells through chimeric an

Targeting of T lymphocytes to melanoma cells through

chimeric anti-GD3 immunolglobulin T-cell receptors

- 일시: 2001년 4월 19일(목요일) 오후 3시

- 연사: 윤 채옥 박사


       (연세대학교 의과대학)

- 장소: 생명관 207호 세미나실

- Abstract


Immunoglobulin T-cell receptors (IgTCRs) combine the specificity of antibodies with the potency of cellular killing by grafting antibody recognition domains onto TCR signaling chains. IgTCR-modified T cells are thus redirected to kill tumor cells based on their expression of intact antigen on cell surfaces, bypassing the normal mechanism of activation through TCR-peptide-major histocompatibility complex (MHC) recognition. Melanoma is one of the most immunoresponsive of human cancers and has served as a prototype for the development of a number of immunotherapies. The target antigen for this study is the ganglioside GD3, which is highly expressed on metastatic melanoma with only minor immunologic cross-reaction with normal tissues. To determine an optimal configuration for therapy, four combinations of IgTCRs were prepared and studied: sFv-ε, sFv-ζ, Fab-ε,  Fab-ζ, These were expressed on the surface of human T cells by retroviral transduction, IgTCR successfully redirected T-cell effectors in an MHC-unrestricted manner, in this case against a non-T-dependent antigen, with specific binding, activation, and cytotoxicity against GD3+melanoma cells. Soluble GD3 in concentrations up to 100mg/ml did not interfere with recognition and binding of membrane-bound antigen. Based on the outcomes of these structural and functional tests, the sFv-ζ, construct was selected for clinical development. These results demonstrate key features that emphasize the potential of anti-GD3 IgTCR-modified autologous T cells for melanoma therapies.

Keyword.: T cell, gene therapy, immunotherapy, signalling

- 문의처: 생명과학과 성영철 교수(☎ 279-2294)